HMG proteins are a group of non-histone DNA-binding proteins, and HMG-1, HMG-2, HMG14, HMG17, HMG-I(Y) and the like are known. HMG have been thought to participate in acceleration of transcription and growth of cells by binding to DNA in the cells. It was proved that amphoterin discovered as a factor which exists on the surface of nerve cells and extends dendrite is HMG-1 that is one of HMG proteins, so that it is suggested that HMG proteins exhibit a wide variety of actions.
Recently, it was reported that HMG-1 is secreted to the outside of the cells and acts as a strong mediator of systemic inflammation reaction and septic shock (Wang et al., (1999), Science, vol. 285, p. 248). That is, if lipopolysaccharide (LPS) is administered to a mouse, HMG-1 level in the serum is drastically increased at 8 to 24 hours after administration and the mouse dies. In case of administering purified HMG-1 together with LPS, these synergistically act and show lethal activity, and the lethal action by LPS is inhibited by administering an anti-HMG-1 antibody, so that it was shown that HMG-1 is an important mediator of endotoxin shock. In patients suffering from sepsis, HMG-1 level is drastically increased, especially where the patient dies. HMG-1 level in blood is also increased in hemorrhagic shock (Ombrellino et al., (1999), Lancet, vol. 354, p. 1446). Further, it has been reported that production of HMG-I(Y) belonging to HMG-1 is induced by stimulation with LPS.
It was observed that in autoimmune hepatitis, inflammatory bowel disease and in systemic rheumatic diseases, autoantibodies to HMG proteins such as HMG-1, HMG-2, HMG-14 and HMG-17 are produced, so that it is suggested that HMG proteins participate in these inflammatory diseases (Sobajima et al., (1997), Clin. Exp. Immunol., vol. 107, p. 135). Further, it has been reported that HMG proteins participate in growth of cancers (Taguchi et al., (2000), Nature, vol. 405, p. 354).
Thus, although HMG proteins have functions which are necessary to the body, in diseases such as sepsis, they are secreted in excess to the outside of the cells to make the disease worse and to make the body die. A candidate of the method for improving the state of the diseases caused by HMG proteins is to administer a drug such as an antibody, which binds to HMG and inhibits its action. However, in view of the fact that HMG proteins have functions which are necessary in the cells and on the surfaces of the cells, it is concerned that administration of a drug inhibiting HMG activity may cause serious side effects. Thus, it is desired to provide means for selectively removing extracellular HMG proteins which are undesirable to the body.
It has been reported that some substances such as heparin and RAGE, in addition to the above-mentioned antibodies, bind to HMG proteins (Hori et al., (1995), J. Biol. Chem. vol. 270, p 25752, and so on). However, it has not hitherto been proposed to use these HMG protein-binding substances for removing HMG proteins from the body, and no materials which can remove HMG proteins from body fluids are known.